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Does journal endorsement of reporting guidelines influence the completeness of reporting of health research? Larissa Shamseer, MSc Clin Epi Reporting Guideline Research Coordinator 11 October 2012, Freiburg, DE

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Page 1: Does journal endorsement of reporting guidelines influence ... · Does journal endorsement of reporting guidelines influence the completeness of reporting of health research? Larissa

Does journal endorsement of reporting

guidelines influence the completeness

of reporting of health research?

Larissa Shamseer, MSc Clin Epi

Reporting Guideline Research Coordinator

11 October 2012, Freiburg, DE

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Project Investigators

• David Moher, OHRI, Canada

• Doug Altman, The EQUATOR Network, Centre for Statistics in

Medicine (CSM), University of Oxford, UK

• Allison Hirst, CSM, University of Oxford, UK

• John Hoey, Queen’s University, Kingston, Canada

• Anita Palepu, St. Paul’s Hospital, Vancouver, Canada

• Ken Schulz, FHI360, North Carolina, USA

• Iveta Simera, The EQUATOR Network, Centre for Statistics in

Medicine (CSM), University of Oxford, UK

• Project Funding: CIHR (FRN 111750)

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Research Staff

Staff Leads: Adrienne Stevens & Larissa Shamseer

Hadeel AlYacoob

Raymond Daniel

Mary Gauthier

Mandi Kaur

Misty Pratt

Kavita Singh

Becky Skidmore

Justin Thielman

Sophia Tsouros

Lucy Turner

Erica Weinstein

Fatemeh Yazdi

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Review Objectives

To evaluate whether journal endorsement of reporting

guidelines influences the completeness of the reported

literature by comparing:

1. Completeness of reporting of studies published in

journals endorsing reporting guidelines before and

after endorsement.

2. Completeness of reporting of studies published in

journals that have and have not endorsed reporting

guidelines.

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Methods

• Search: (1) reporting guidelines (2) evaluations of RGs

• Screening: determine relevant evaluations, journal

endorsement status for comparisons

• Validity assessment: 6 pre-specified criteria

• Outcome extraction and analyses

• obtain data for all included studies

• Completeness of reporting – RRs/SMDs (99% CIs),

where possible

(by item, total score, flow diagram, descriptive)

• Methodological quality - narrative

• Unwanted effects - narrative

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Methods (2)

• Statistical heterogeneity: I2 statistic

• Subgroup analyses:

• Extent of endorsement

• Variations in checklist items

• Official and unofficial extensions

• Sensitivity analyses:

• Six-month endorsement period

• Study outliers

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Eligibility criteria - inclusions

• Primary intent: completeness of reporting

• Exclude methodologic quality / quality assessment

• Exclude SRs addressing clinical Q

• Evaluates one of 101 RGs of interest

• Exclude those that do not explicitly state assessing RG

• At least one study in journal that endorses RG

• Exclude evaluations of conference abstracts

• Contacted authors

• Follow-up with journals

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Eligibility criteria - exclusions

• Inappropriate use of RG

• Eg, STROBE for abstracts

• Eg, STARD for reviews

• Assesses studies before RG published

• Eg, used PRISMA on reviews published before 2009

• Interrupted series designs, controlled before-after

analyses

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PRISMA flow - Included RGs

• General – 5

• Animal – 2

• Basic science – 1

• Lab/pre-clinical – 10

• Case reports – 1

• Observational – 9

• Non-randomized – 1

• Prospective studies – 5

• General, clinical trials – 14

• Various content areas – 13

• RCTs – 18

• RCT + observational – 1

• RCTs, quasi, SRs, m/a – 1

• SRs + m/a – 3

• Diagnostic studies – 4

• Economics – 5

• Evaluation studies – 2

• Qualitative – 2

• QI studies – 1

• Standardized patient reports – 1

• Methodology – 1

• Validation studies – 1

98 potential RGs

(EQUATOR search)

76 excluded

• Not reporting guidance (12)

• Methods not described (56)

• Not explicitly consensus–based (4)

• Duplicates/companion reports (3)

• CONSORT (1) 79 RGs (Moher 2011) 22 RGs +

101 included RGs

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PRISMA flow –

Included Evaluations

Records screened (n = 15240) Records excluded (n = 14096)

Full-text - round 1 (n = 1144) Full-text excluded, with reasons (n = 826)

Full-text - round 2 (n = 318) Full-text excluded, with reasons (n = 159)

Duplicate & multiple reports quarantined (n=22)

Contact authors & journals / Modified checklists (n = 159)

Full-text excluded, with reasons (n = 139)

Included (n=20)

Other source records (n = 40)

Database records (n = 17225)

After duplicates removed (n = 15262)

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Included (n=20)

Included studies table only

(n=10) Analysis (n=10)

(7/101 RGs evaluated)

Final included

evaluations

1. CONSORT for harms, 2004 (n=3): Haidich 2011, Turner 2011, Lee 2008

2. CONSORT for herbal medicines, 2006 (n=1): Ernst 2011

3. BMJ economic checklist, 1996 (n=2): Herman 2005, Jefferson 1998

4. QUOROM, 1999 (n=3): Hind 2007, Biondi Zoccai 2006, Poolman 2007

5. STARD, 2003 (n=8): Freeman 2009, Mahoney 2007, Selman 2011, Smidt

2006, Coppus 2006, Johnson 2007, Krzych 2009, Paranjothy 2007

6. STRICTA, 2002 (n=1): Hammerschlag 2011

7. STROBE, 2007 (n=2): Parsons 2011, Delaney 2010

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Characteristics of studies

• 7 countries:

• UK, US, Canada, Netherlands, Greece, Italy, Poland

• Study funding:

• Not reported, Government, Charity, Industry, No funding,

Other

• Range of interventions

• Diagnostic studies, Complementary medicine, Drug

therapies, Therapeutic interventions (general), Surgery,

Biochem and Lab Methods, Unspecified

• Range of medical specialties

• Unspecified, Medicine (General/Internal), Obstet/Gyne,

Orthopedics, Cardiac/Cardiovascular, Endocrinology &

Metabolism, Hematology, Neurology, Reproductive,

Urology/Nephrology

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Included evaluations

Guideline Endorsers v. Non-endorsers Before v. After Endorsement

# evals # journals # studies # evals # journals # studies

BMJ econ 2 2 vs. 11 3 vs. 16 1 1 1 vs. 8

CONSORT

- Harms

3 8 vs. 108 31 vs. 267 1 1 1 vs. 2

CONSORT

- Herbals

1 1 vs. 3 1 vs. 4 - - -

QUOROM 2 2 vs. 11 2 vs. 12 1 1 13 vs. 15

STARD 8 26 vs. 71 133 vs.

168

2 8 98 vs. 79

STRICTA

(2002)

1 3 vs. 64 17 vs. 129 1 2 11 vs. 4

STROBE 2 3 vs. 9 10 vs. 42 1 2 9 vs. 11

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Endorser vs. Non-endorser

BMJ Economics guidelines

Item # studies Risk ratio and 99% CI (Random)

RR (99%CI)

Economic importance of question 1 13 1.18 (0.52, 2.67)

Clearly describe comparisons 1 13 1.18 (0.52, 2.67)

Form of economic evaluation 1 13 2.86 (0.75, 10.89)

Justify choice of economic evaluation 1 13 1.33 (0.03, 63.52)

Source(s) of effectiveness estimates 1 13 1.00 (0.51, 1.97)

Design and results of effectiveness study (single study) 1 12 1.00 (0.50, 1.99)

Primary economic evaluation outcome measure(s) 1 13 0.95 (0.46, 1.96)

Subjects from whom valuations obtained 1 4 3.00 (0.08, 114.59)

Quantities of resources separate from unit costs 1 13 3.00 (0.12, 77.64)

Methods for estimating quantities and unit costs 1 13 1.05 (0.49, 2.26)

Currency of price adjustments for inflation or currency conversion 1 13 6.67 (0.84, 53.19)

Time horizon of costs and benefits 1 13 1.00 (0.51, 1.97)

Statistical tests and CIs for stochastic data 1 12 1.00 (0.50, 1.99)

Compare relevant alternatives 1 13 1.38 (0.17, 11.13)

Incremental analysis 1 4 1.67 (0.33, 8.48)

Major outcomes in aggregated and dissaggregated forms 1 13 0.95 (0.46, 1.96)

Answer to study question 1 13 1.05 (0.49, 2.26)

Conclusions follow from data 1 13 1.00 (0.51, 1.97)

Conclusions with appropriate caveats 1 13 0.61 (0.10, 3.82)

0.1 0.2 0.5 1 2 5 10

Favours

non-endorsement

Favours

endorsement

# evals

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Endorser vs. Non-endorser

CONSORT for Harms

Item # evals Risk ratio and 99% CI (Random) RR (99%CI)

Title or abstract 1 102 0.94 (0.66, 1.34)

Introduction 1 102 1.00 (0.54, 1.85)

Outcomes - List adverse events and definitions 2 296 1.24 (0.42, 3.64)

Outcomes - How information collected 2 296 1.18 (0.95, 1.46)

Statistical methods - Plans for presenting/analyzing harms 2 296 0.89 (0.45, 1.78)

Participant flow 2 296 0.90 (0.47, 1.72)

Numbers analyzed 2 296 0.98 (0.68, 1.41)

Absolute risk for each adverse event and appropriate metrics 1 102 0.98 (0.79, 1.22)

Subgroup and exploratory analyses 1 102 0.98 (0.38, 2.53)

Discussion 1 102 1.08 (0.85, 1.37)

0.1 0.2 0.5 1 2 5 10

Favours

non-endorsement

Favours

endorsement

# studies

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Endorser vs. Non-endorser

STARD

Item # evals # studies Risk ratio and 99% CI (Random) RR ( 99% CI)

Title, abstract, keywords 2 62 1.03 (0.49, 2.15)

Introduction 3 88 1.07 (0.82, 1.39)

Participants - Study population 3 88 1.36 (0.56, 3.34)

Participants - Recruitment 3 88 1.07 (0.68, 1.68)

Participants - Sampling 3 88 0.73 (0.41, 1.28)

Participants - Data collection 3 88 0.94 (0.74, 1.19)

Test methods - Reference standard 3 88 1.03 (0.81, 1.33)

Test methods - Technical specifications 2 38 1.00 (0.61, 1.64)

Test methods - Readers blinded to other result? 2 38 0.83 (0.02, 42.02)

Statistical methods - Measures and uncertainty 2 60 2.19 (0.93, 5.14)

Statistical methods - Test reproducibility 2 38 0.56 (0.12, 2.64)

Results - Recruitment 3 87 0.83 (0.54, 1.28)

Results - Participant characteristics 3 88 1.77 (1.16, 2.71)

Results - Participant flow 4 227 1.35 (0.84, 2.17)

Results - Time interval from test to reference 3 88 0.51 (0.20, 1.32)

Results - Disease severity 3 88 0.73 (0.08, 6.84)

Results - Cross-tabulation of test by reference results 3 88 1.28 (0.70, 2.34)

Results - Any adverse events 3 68 1.42 (0.34, 6.03)

Results - Diagnostic accuracy estimates and uncertainty 2 60 1.82 (0.95, 3.50)

Results - How indeterminate results, missing data, outliers handled 3 79 1.44 (0.86, 2.41)

Results - Variability between subgroups 2 29 1.32 (0.75, 2.31)

Results - Test reproducibility 2 38 0.56 (0.12, 2.64)

Discussion 3 88 1.00 (0.89, 1.12)

0.1 0.2 0.5 1 2 5 10

Favours

non-endorsement

Favours

endorsement

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Endorser vs. Non-endorser

STROBE

Item # evals Risk ratio and 99% CI (Random)

Title or Abstract 1 47 0.40 (0.08, 2.09)

Abstract 1 47 1.02 (0.73, 1.43)

Introduction - Background and rationale 1 47 1.02 (0.82, 1.26)

Introduction - Objectives 1 47 1.09 (0.64, 1.86)

Methods - Study design 1 47 0.94 (0.68, 1.29)

Methods - Setting, location, dates 1 47 1.06 (0.53, 2.11)

Methods - Participants eligibility 1 47 0.99 (0.71, 1.39)

Methods - Participant matching 1 24 1.50 (0.55, 4.10)

Methods - Outcome, exposure, other variables 1 47 0.88 (0.38, 2.03)

Methods - Data sources and measurement 1 47 0.91 (0.67, 1.24)

Methods - Addressing sources of bias 1 47 0.84 (0.15, 4.87)

Methods: - Study size 1 47 1.58 (0.73, 3.43)

Methods - Handling of quantitative variables 1 47 0.92 (0.56, 1.51)

Methods - Statistical methods 1 47 0.92 (0.56, 1.51)

Methods - Subgroups and interactions 1 47 1.54 (0.48, 4.93)

Methods - Loss to follow-up, matching, sampling 1 42 0.81 (0.14, 4.76)

Methods - Sensitivity analyses 1 47 1.21 (0.19, 7.53)

Results - Participant flow 1 47 0.99 (0.71, 1.39)

Results - Reasons for nonparticipation 1 47 0.84 (0.06 , 12.01)

Results - Flow diagram 1 47 2.81 (0.33 , 24.14)

Results - Participant characteristics 1 47 1.61 (0.99, 2.61)

Results - Missing data 1 47 0.70 (0.13, 3.93)

Results - Follow-up time (cohort studies) 1 10 1.08 (0.56, 2.08)

Results - Outcome data 1 47 0.95 (0.58, 1.56)

Results - Estimates and precision 1 47 0.82 (0.43, 1.56)

Results - Boundaries for continuous variable categories 1 44 0.49 (0.04, 6.27)

Results - Translating relative into absolute risk estimates 1 35 1.04 (0.02 , 61.88)

Results - Other analyses 1 46 1.23 (0.30, 5.02)

Discussion - Key results 1 47 0.99 (0.81, 1.21)

Discussion - Limitations 1 47 1.51 (1.05, 2.18)

Discussion - Interpretation 1 47 1.26 (0.93, 1.70)

Discussion - Generalizability 1 47 1.35 (0.88, 2.07)

Other - Funding 1 47 1.47 (0.93, 2.32)

0.1 0.2 0.5 1 2 5 10

Favours

non-endorsement

Favours

endorsement

RR (99% CI) # studies

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Endorser vs. Non-endorser

Total sum score of items

Guideline Evaluation Studies SMD (99% CI)

BMJ economics

guideline, 1996

1 2 vs. 11 3.47 (0.58 to 6.35)

CONSORT for

harms, 2004

2 30 vs. 266 -0.06 (-0.59 to 0.47)

STARD, 2003 3 88 0.55 (-0.08 to 1.18)

STRICTA, 2002 1 17 vs. 129 1.35 (-0.11 to 2.81)

STROBE, 2007 1 9 vs. 38 0.33 (-0.63 to 1.29)

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After vs. Before Endorsement

QUOROM

Item # studies Risk ratio and 99% CI (Random)

RR (99%CI)

Flow diagram 1 28 1.01 (0.41, 2.49)

0.1 0.2 0.5 1 2 5 10

Favours

non-endorsement

Favours

endorsement

# evals

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After vs. Before Endorsement

STARD

Item # studies Risk ratio and 99% CI (Random) RR (99%CI)

Flow diagram 1 173 11.49 (0.82 ,160.60)

0.01 0.1 1 10 100

Favours

non-endorsement

Favours

endorsement

# evals

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After vs. Before Endorsement

STROBE

Item # evals # studies Risk ratio and 99% CI (Random) RR (99% CI)

Title or Abstract 1 20 1.22 (0.12, 12.20)

Abstract 1 20 0.98 (0.66, 1.45)

Introduction - Background and rationale 1 20 1.00 (0.78, 1.28)

Introduction - Objectives 1 20 0.86 (0.51, 1.45)

Methods - Study design 1 20 0.89 (0.61, 1.29)

Methods - Setting, location, dates 1 20 1.83 (0.56, 6.05)

Methods - Participants eligibility 1 20 0.89 (0.61, 1.29)

Methods - Participant matching 1 15 1.00 (0.38, 2.62)

Methods - Outcome, exposure, other variables 1 20 0.76 (0.31, 1.88)

Methods - Data sources and measurement 1 20 0.98 (0.66, 1.45)

Methods - Addressing sources of bias 1 20 0.81 (0.11, 6.31)

Methods: - Study size 1 20 1.83 (0.56, 6.05)

Methods - Handling of quantitative variables 1 20 0.86 (0.51, 1.45)

Methods - Statistical methods 1 20 1.07 (0.55, 2.08)

Methods - Subgroups and interactions 1 20 4.89 (0.35, 68.31)

Methods - Loss to follow-up, matching, sampling 1 19 0.74 (0.10, 5.65)

Methods - Sensitivity analyses 1 20 2.44 (0.13, 45.99)

Results - Participant flow 1 20 1.09 (0.68, 1.75)

Results - Reasons for nonparticipation 1 20 3.60 (0.06, 208.53)

Results - Flow diagram 1 20 6.00 (0.13 , 277.77)

Results - Participant characteristics 1 20 1.63 (0.75, 3.53)

Results - Missing data 1 20 6.00 (0.13, 277.77)

Results - Follow-up time (cohort studies) 1 5 1.00 (0.44, 2.28)

Results - Outcome data 1 20 0.86 (0.51, 1.45)

Results - Estimates and precision 1 20 0.68 (0.37, 1.25)

Results - Boundaries for continuous variable categories 1 20 0.41 (0.03, 6.31)

Results - Translating relative into absolute risk estimates 1 18 0.41 (0.01, 23.24)

Results - Other analyses 1 20 0.92 (0.19, 4.48)

Discussion - Key results 1 20 1.00 (0.78, 1.28)

Discussion - Limitations 1 20 1.34 (0.80, 2.24)

Discussion - Interpretation 1 20 1.09 (0.78, 1.53)

Discussion - Generalizability 1 20 0.98 (0.66, 1.45)

Other - Funding 1 20 1.40 (0.72, 2.72)

0.1 0.2 0.5 1 2 5 10

Favours

non-endorsement

Favours

endorsement

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After vs. before endorsement

Total sum score of items

Guideline Evaluation Studies SMD (99% CI)

STRICTA,

2002

1 11 vs. 4 0.63 (-0.91 to 2.17)

STROBE, 2007 1 9 vs. 11 0.26 (-0.90 to 1.42)

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Secondary outcomes

• Methodological quality of evaluations’ included studies

• 6 of 20 studies reported information

• 2 studies used Oxman-Guyatt

• 1 studies used Cochrane Risk of Bias tool

• 1 study assessed generalizability and reporting

• 1 study used QUADAS but could not extract as per

our comparisons

• 1 study assessed internal and external validity

• Unwanted effects from use of guideline

• No studies assessed

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Results

• Only 7/101 RGs evaluated

• Few existing evaluations, each assessing completeness

of reporting of a small number of studies; subgroup &

sensitivity analyses not possible

• Few studies assessed methodological quality

• No studies assessed unwanted effects

vs.

• CONSORT SR (50 evaluations, >16000 RCTs)

• 25 of 27 items favoured endorsement vs. non-

endorsement with 5 items statistically significant

• 5 items stat sig for after-before endorsement

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Strengths and Limitations

• Strengths:

• First cumulative evaluation of RG effectiveness

• Used best comparisons from CONSORT SR

• Reworked authors’ data to enable comparisons

• Limitations:

• Were all potential evaluations located?

• For some, ‘partial’ reporting may have been included

in ‘complete’ data by authors

• Not able to obtain all data – authors’ availability to

answer queries, some items considered ‘not

applicable’

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Discussion

• Why so few evaluations?

• We couldn’t put a drug to market without evaluating it!

• Potentially more evaluations that we wished to

include, but could not

• What is the intervention?

• Journal endorsement (not just guideline publication) is

where the rubber-meets-the-road

• Extent of endorsement – needs to be clear and have

an implementation strategy

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28

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Changes from protocol

• Did not include CONSORT

• Refer to CONSORT SR

• Did not include variations in checklist items

• Changes to validity assessment

• 2 items clarified wording

• Confounding

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Collate reports / Contact authors,

journals/ Assess modified

checklists (n=159)

Full-text excluded (n=139): • Evaluates CONSORT (n=45) • Multiple report of excluded study (n=27) • No response from author to determine eligibility (n=19) • No journals endorsed the RG (n=14) • Authors used modified checklist (n=9) • List of studies or journals not provided (n=6) • Inappropriate use of RG (n=3) • Comparison not possible given study dates and endorsement information (n=3) • Assessed studies before RG published (n=2) • Full report or information not in English or French (n=2) • Could not locate author contact information (n=2) • All journals endorsed the RG, comparison not relevant (n=2) • Did not address completeness of reporting (n=1) • Full report or information not available from the author (n=1) • Reporting guideline publication (n=1) • Could not locate journal website or instructions to authors (n=1) • Not comparison of interest (n=1)

Included (n=20)

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Validity – Endorsing vs Non-endorsing Author, Year Studies Two or more

assessors for

reporting

No evidence

of selective

reporting

Comprehensive

search strategy

Balance of

studies per

journal

BMJ economic guidelines, 1996

Herman, 2005 2 vs. 11 Unclear High Low High

Jefferson, 1998 1 vs. 5 Unclear Unclear High High

CONSORT extension for harms, 2004

Haidich, 2011 25 vs. 77 High High High Low

Lee, 2008 1 vs. 1 High High High High

Turner, 2011 5 vs. 189 Low High Low Low

CONSORT extension for herbal interventions, 2006

Ernst, 2011 1 vs. 4 Unclear High Low High

QUOROM, 1999

Biondi-Zoccai, ‘06 1 vs. 6 High High High High

Poolman, 2007 1 vs. 6 High Unclear Low High

STRICTA, 2002

Hammerschlag, ‘11 17 vs. 129 Low High Low Unclear

STROBE, 2007

Delaney, 2010 1 vs. 4 High Unclear Low High

Parsons, 2011 9 vs. 38 Low Unclear Low Low

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Validity – Endorsing vs Non-endorsing

Author, Year Studies Two or more

assessors for

reporting

No evidence

of selective

reporting

Comprehensive

search strategy

Balance of

studies per

journal

STARD, 2003

Coppus, 2006 8 vs. 19 Low High Low High

Freeman, 2009 3 vs. 9 Unclear High High High

Johnson, 2007 1 vs. 10 High High Low High

Krzych, 2009 4 vs. 21 Unclear High Low High

Mahoney, 2007 6 vs. 20 High High Low High

Paranjothy, 2007 1 vs. 8 High High Low High

Selman, 2011 15 vs. 35 High Low Low Low

Smidt, 2006 95 vs. 46 High High Low Low

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Validity – After vs. before endorsement

Author, Year Studies Two or more

assessors for

reporting

No evidence

of selective

reporting

Comprehensive

search strategy

Balance

of studies

per

journal

Sampling

took place

after RG

publication

BMJ economic guidelines, 1996

Jefferson, 1998 1 vs. 8 Unclear Unclear High High High

CONSORT extension for harms, 2004

Lee, 2008 1 vs. 2 High High High Low Low

QUOROM, 1999

Hind, 2007 13 vs. 15 Low High Unclear High High

STARD, 2003

Selman, 2011 3 vs. 1 High Low Low Low High

Smidt, 2006 95 vs. 78 High High Low Low Low

STRICTA, 2002

Hammerschlag,

2011 11 vs. 4 Low High Low High Low

STROBE, 2007

Parsons, 2011 9 vs. 11 Low Unclear Low Low Low

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CONSORT SR – by item

Endorser vs. Non After vs. Before

CONSORT Checklist Item # of Evals

# of RCTs

Pooled Risk ratios and 99% CI

RR 99% CI

Title and Abstract 3 532 1.41 (0.63, 3.16) Introduction 2 457 1.04 (1.00, 1.08) Participants 4 622 0.98 (0.88, 1.09) Interventions 4 630 1.02 (0.97, 1.07) Objectives 2 517 1.04 (0.91, 1.18) Outcomes 5 716 1.43 (0.85, 2.40) Sample Size 6 983 1.30 (0.71, 2.37) Sequence Generation 8 1,085 1.46 (0.88, 2.44) Allocation Concealment 6 855 1.23 (0.55, 2.75) Implementation 2 517 1.94 (0.15, 24.7) Blinding of Paticipants 1 75 0.77 (0.45, 1.31) Blinding of Intervention 1 75 0.26 (0.09, 0.74) Blinding of Outcome Assessor 1 75 0.66 (0.34, 1.30) Blinding of Data Analyst 1 75 0.27 (0.02, 3.71) Blinding Any description 4 926 0.96 (0.61, 1.51) Statistical Methods 5 1,111 0.86 (0.62, 1.19) Participant Flow 8 992 1.33 (0.95, 1.87) Recruitment 3 828 1.77 (0.48, 6.49) Baseline Data 2 529 1.42 (1.24, 1.62) Numbers Analysed 6 1,005 1.72 (1.18, 2.50) Outcomes and Estimation 3 532 1.35 (0.73, 2.50) Ancillary Analyses 1 442 3.46 (2.47, 4.84) Adverse Events 3 507 1.39 (1.12, 1.73) Interpretation 1 442 1.01 (0.98, 1.04) Generalisability 1 442 1.77 (2.12, 1.48) Overall Evidence 2 517 1.31 (0.99, 1.73)

0.5 1 2

Favours non-endorsement

Favours endorsement

# of Evals

# of RCTs

Pooled Risk ratios and 99% CI

RR 99% CI

7 1,233 1.13 (0.96, 1.33) 5 513 1.07 (1.01, 1.14) 6 683 0.95 (0.56, 1.62) 6 638 1.00 (0.95, 1.05) 5 540 1.01 (0.96, 1.06) 8 1,302 1.17 (0.95, 1.44) 11 1,843 1.61 (1.13, 2.29) 14 2,231 1.59 (1.38, 1.84) 16 2,396 1.81 (1.25, 2.62) 5 498 1.47 (0.65, 3.32) 5 711 1.39 (0.87, 2.22) 5 710 1.25 (0.74, 2.12) 5 719 1.72 (0.69, 4.30) 3 497 3.56 (0.40, 31.8) 8 1,851 1.23 (0.93, 1.62) 9 894 1.03 (0.90, 1.18) 16 2,461 1.16 (0.94, 1.44) 6 959 1.03 (0.75, 1.41) 5 529 1.07 (0.94, 1.22) 13 2,145 1.23 (0.98, 1.55) 6 617 1.00 (0.95, 1.05 4 378 1.31 (0.48, 3.58) 8 911 1.14 (0.86, 1.52) 5 540 1.01 (0.96, 1.06) 5 540 1.22 (0.88, 1.70) 4 317 1.03 (0.91, 1.17)

0.5 1 2

Favours non-endorsement

Favours endorsement

• Stat sig: Introduction, Baseline data, Numbers

analyzed, Ancillary analyses, Adverse events,

Generalizability, Sum score

• Stat sig: Alloc conceal, Introduction,

Sample size, Sequence generation,

Sum score